ライフサイエンスコーパス: apoptosome

1 manipulated by interactions upstream of the apoptosome.

2 elease, which nucleates the Apaf-1/caspase-9 apoptosome.

3 modifications or by direct activation of the apoptosome.

4 a caspase-activating structure known as the apoptosome.

5 ows activation of this hybrid caspase by the apoptosome.

6 a polymeric activation platform known as the apoptosome.

7 ase to the cytoplasm, thereby activating the apoptosome.

8 ay instead form a holoenzyme with the Apaf-1 apoptosome.

9 mosin alpha (ProTalpha), an inhibitor of the apoptosome.

10 he Dark complex may represent the Drosophila apoptosome.

11 -activating heptameric protein complex named apoptosome.

12 agmentation initiated by activated cell-free apoptosome.

13 f one or at most, two pc-9 dimers per active apoptosome.

14 paf-1) in an oligomeric complex known as the apoptosome.

15 n induce their activation independent of the apoptosome.

16 in association of Apaf-1 into the functional apoptosome.

17 0) cleavage on caspase-9 activity within the apoptosome.

18 cleavage on XIAP-mediated inhibition of the apoptosome.

19 e is a diminished amount of caspase-9 in the apoptosome.

20 ot correlate with functional activity of the apoptosome.

21 ubstituted for wild-type procaspase-9 in the apoptosome.

22 by a multimeric adaptor complex known as the apoptosome.

23 ruited to, activated and retained within the apoptosome.

24 igomerization of Apaf-1 and formation of the apoptosome.

25 ptotic protease-activating factor-1 (APAF-1) apoptosome.

26 ficiency of Apaf-1, a critical member of the apoptosome.

27 of a multimeric Apaf-1.cytochrome c complex, apoptosome.

28 plex, further assembly occurs to produce the apoptosome.

29 o the activation of initiator caspase by the apoptosome.

30 event the oligomerization of Apaf-1 into the apoptosome.

31 activation of a caspase-9/Apaf1/cytochrome c apoptosome.

32 changes that results in the formation of the apoptosome.

33 well as the molecular timer function of the apoptosome.

34 ing that of Apaf-1, the major protein in the apoptosome.

35 uld no longer be adequately activated by the apoptosome.

36 some but prevents apoptotic functions of the apoptosome.

37 processing, suggesting that M1 targeted the apoptosome.

38 ric disk is formed on the central hub of the apoptosome.

39 evealing a new regulatory axis affecting the apoptosome.

40 ein modifications occurring in reconstituted apoptosomes.

41 ermeabilization, leading to formation of the apoptosome, a caspase activation complex.

42 olecular Cell describes the structure of the apoptosome, a multicomponent death machine, deciphered b

43 The protease caspase-9 is activated on the apoptosome, a multiprotein signal transduction platform

44 th Hofmeister salts and a reconstituted mini-apoptosome activate caspase-9 by a second-order process,

45 Therefore, in addition to dimerization, the apoptosome activates caspase-9 by enhancing its affinity

46 The mechanism by which the apoptosome activates caspases during apoptosis has been

47 conferred resistance to cytochrome c-induced apoptosome activation in normal cells, reflecting enhanc

48 Dysfunctional apoptosome activation may contribute both to the pathoge

49 , normally at high mM concentrations, affect apoptosome activation remains unclear.

50 also exhibit defects in cytochrome c-induced apoptosome activation, further promoting chemotherapeuti

51 are the first to show that IAP function and apoptosome activity are coupled in cells.

52 in a significant increase (up to 8-fold) in apoptosome activity compared with p35/p12.

53 This dysfunctional apoptosome activity was not explained by reduced express

54 ovarian cancer cell line with dysfunctional apoptosome activity, retains the ability to form the Apa

55 ovarian carcinoma cell line with diminished apoptosome activity, was significantly more resistant to

56 af-1, resulting in a significant decrease in apoptosome activity.

57 r, the determinants that specify whether the apoptosome acts to kill or remodel have yet to be identi

58 Both caspases were activated by the apoptosome after irradiation.

59 irectly inhibits caspase-7 activation by the apoptosome and also forms a stable approximately 200-kDa

60 A direct comparison of Apaf-1 in the apoptosome and as a monomer reveals conformational chang

61 with oligomerized processed caspase-9 in the apoptosome and blocks procaspase-3 activation.

62 iting the activation of caspase-3 within the apoptosome and by preventing release of active caspase-3

63 dria and cytochrome C in the assembly of the apoptosome and caspase activation has been established f

64 ocaspase-9 possessed higher affinity for the apoptosome and could displace the processed caspase-9 fr

65 s at the levels of both the Apaf-1-caspase-9 apoptosome and effector caspases.

66 activation of caspase-9 and formation of the apoptosome and efficient apoptosis signaling.

67 HtrA2, active caspase-7 is released from the apoptosome and forms a stable approximately 200-kDa XIAP

68 ced procaspase-9 activation, both within the apoptosome and in artificial systems, requires stable ho

69 nin inhibits stress-induced formation of the apoptosome and increases the interaction of small RNAs w

70 ults in the formation of an Apaf-1-caspase-9 apoptosome and induces the apoptotic protease cascade by

71 itiator caspase-9 is activated by the Apaf-1 apoptosome and must remain bound to retain significant c

72 1 CARDs recruit 3 to 5 pc-9 molecules to the apoptosome and one catalytic domain may be parked on the

73 M1 interacts with the apoptosome and prevents procaspase-9 processing as well

74 inds activated caspase-3 produced within the apoptosome and sequesters it within the complex.

75 mitochondria, allowing for formation of the apoptosome and subsequent cleavage and activation of cas

76 that are essential for the formation of the apoptosome and the activation of caspase-9.

77 molecular research, the assembly of the holo-apoptosome and the process of caspase-9 activation remai

78 red activator of Apaf-1 for formation of the Apoptosome and thereby activation of caspase-9 (Csp9).

79 This study identified APAF-1 apoptosome and XIAP as intracellular targets of P. gingi

80 Cytoplasmic cytochrome c completes the apoptosome, and activated caspase 9 and 3 were present i

81 pneumophila modulates the inflammasome, the apoptosome, and NF-kappaB pathway simultaneously.

82 Here, we establish that a component of the apoptosome, and pivotal regulator of apoptosis, is also

83 eased dramatically upon association with the apoptosome, and the apoptosome bound caspase-9 is the ca

84 fied as key triggers of apoptosis, including apoptosome apoptotic peptidase activating factor 1 (APAF

85 e-3, procaspase-9 cannot be processed by the apoptosome as a typical substrate.

86 propose that Tango7 specifies the Drosophila apoptosome as an effector of cellular remodeling.

87 Regulation of apoptosome assembly by other cellular factors is poorly

88 susceptibility protein (CAS) can facilitate apoptosome assembly by stimulating nucleotide exchange o

89 Apoptosome assembly is highly regulated in the intrinsic

90 rmeabilization (MOMP), cytochrome c release, apoptosome assembly, and caspase activation.

91 Cytochrome c is a critical regulator of apoptosome assembly, caspase activation, and programmed

92 ion by abrogating Apaf-1 oligomerization and apoptosome assembly.

93 a procaspase-9 CARD either before or during apoptosome assembly.

94 apoptotic pathways and can serve as sites of apoptosome assembly.

95 create an extended Apaf-1 monomer and drive apoptosome assembly.

96 These changes occur before the apoptosome-associated pro-caspase-9 cleavage.

97 of the novel antiapoptosis effects of M1 via apoptosome association will be helpful for understanding

98 t an atomic structure of an intact mammalian apoptosome at 3.8 A resolution, determined by single-par

99 eolytic processing is mediated by the Apaf-1 apoptosome at the onset of apoptosis.

100 activated allosterically upon binding to the apoptosome backbone, the mathematical simulations quanti

101 s activated allosterically by binding to the apoptosome backbone.

102 unit of the caspase-9 apoptosome facilitates apoptosome blockade.

103 pon association with the apoptosome, and the apoptosome bound caspase-9 is the caspase-9 holoenzyme (

104 esolution, the cryo-EM structure of the Dark apoptosome bound to the caspase recruitment domain (CARD

105 ociates with and allows the formation of the apoptosome but prevents apoptotic functions of the apopt

106 alcium ion negatively affect the assembly of apoptosome by inhibiting nucleotide exchange in the mono

107 t common effector pathways, regulated by the apoptosome, can underlie morphologically distinct forms

108 caspase activity and localizes to the active apoptosome compartment via its C terminus.

109 tly via assembly of a cytochrome c-dependent apoptosome complex containing caspase-9 and apoptotic pr

110 Is there a suborganellar apoptosome complex effecting the integration of death si

111 ystal structure of a funnel-shaped octameric apoptosome complex from the nematode Caenorhabditis eleg

112 also inhibits Apaf-1 oligomerization into an apoptosome complex in a purely reconstituted system.

113 e now characterized the caspase-7 activating apoptosome complex in MCF-7 cell lysates activated with

114 Thus, the assembly and activation of the apoptosome complex in the cell requires the rapid and ex

115 apoptosis) binds tightly to caspase-9 in the apoptosome complex, and as a result caspase-7 processing

116 al release of cytochrome c, formation of the apoptosome complex, and caspase activation.

117 cell against inappropriate formation of the apoptosome complex, caused by the inadvertent release of

118 of cytochrome c and activation of the Apaf-1 apoptosome complex, which initiates the caspase cascade.

119 This approximately 700-kDa apoptosome complex, which is also formed in apoptotic MC

120 ive caspase-processing approximately 700-kDa apoptosome complex, which predominates in apoptotic cell

121 in the formation of the approximately 700-kd apoptosome complex, which recruits and processes caspase

122 ic Apaf-1 in a approximately 1.4-2.0 mDa pre-apoptosome complex.

123 ation of Apaf-1 to form a caspase-activating apoptosome complex.

124 ation of Apaf-1 into an approximately 700-kd apoptosome complex.

125 the assembly of the large Apaf-1 containing apoptosome complex.

126 ating factor 1 (Apaf-1)/caspase-9 containing apoptosome complex.

127 wing heat shock, functional Apaf-1.caspase-9 apoptosome complexes were not formed, and caspase-9 was

128 roximately 1.4-MDa and approximately 700-kDa apoptosome complexes, and the latter complex directly cl

129 s mediated by transcriptional suppression of apoptosome components Apaf-1 and procaspase-9, and limit

130 ected in HCMV-infected cells, association of apoptosome components was not.

131 cholesterol affinity, association of Bax and apoptosome components with MAM lipid rafts.

132 Furthermore, orthologues of the apoptosome components, Ark (Apaf-1) and Dronc (caspase-9

133 we describe knockout and knockin studies of apoptosome components, elegant structural and biochemica

134 fore provides novel mechanistic insight into apoptosome-dependent apoptosis execution and suggests th

135 spases, from an apoptosome-independent to an apoptosome-dependent pathway.

136 a near atomic structure of the active human apoptosome determined by cryo-electron microscopy.

137 sion does not affect cytochrome c release or apoptosome-driven caspase-9 activation, but instead inhi

138 he motif of the p12 subunit of the caspase-9 apoptosome facilitates apoptosome blockade.

139 Processed caspase-9 and the apoptosome form a holoenzyme with robust proteolytic act

140 tors by functioning as natural inhibitors of apoptosome formation and a barrier that cells must overc

141 edes the ability of cytochrome c to nucleate apoptosome formation and activate downstream caspases.

142 lex involving Cyt c and tiRNAs that inhibits apoptosome formation and activity.

143 nteractions and proteolytic processes during apoptosome formation and apoptosis execution and conduct

144 nosine 5'-triphosphate), was able to support apoptosome formation and caspase activation in place of

145 In apoptosis, apoptosome formation and caspase activity were observed

146 vels of nucleotides inhibit the CC-initiated apoptosome formation and caspase-9 activation by directl

147 le in many forms of apoptosis by stimulating apoptosome formation and subsequent caspase activation.

148 The inhibitory effects of K(+) on apoptosome formation are antagonized in a concentration-

149 promote cell survival by preventing MOMP or apoptosome formation as well as via regulation of Akt an

150 PETCM relieved ProT inhibition and allowed apoptosome formation at a physiological concentration of

151 at BETT relieved ProT-mediated inhibition of apoptosome formation by blocking the interaction between

152 Our analysis suggests that cooperative apoptosome formation is a mechanism for inducing bistabi

153 mathematical modeling, that cooperativity in apoptosome formation is critically important for determi

154 over, juxtapositioning of Apaf-1 monomer and apoptosome formation occur about 5h earlier than the app

155 Cytochrome c (CC)-initiated Apaf-1 apoptosome formation represents a key initiating event i

156 , enhances caspase-9 activation by promoting apoptosome formation through an unknown mechanism.

157 poptosis based on Apaf-1 oligomerization and apoptosome formation using the split luciferase strategy

158 ochrome c or delay in ATP increase attenuate apoptosome formation, and caspase activation thereby dis

159 detected in time of cytochrome c appearance, apoptosome formation, and caspase activity upon inductio

160 p53 expression, cytochrome c release, apoptosome formation, and caspase-3/7 activation are obs

161 proteins promoted caspase-9 activation after apoptosome formation, whereas ProT negatively regulated

162 xchange on Apaf-1 are two required steps for apoptosome formation.

163 the roles of Bax, Bcl-2, and MPTP vis-a-vis apoptosome formation.

164 regulated caspase-9 activation by inhibiting apoptosome formation.

165 c) release from mitochondria and subsequent apoptosome formation.

166 icroscopic (cryo-EM) structure of the intact apoptosome from Drosophila melanogaster at 4.0 A resolut

167 The ability of NAC to enhance Apaf1-apoptosome function reveals a novel paradigm for apoptos

168 importance of oxidative phosphorylation and apoptosome function to both the intrinsic and extrinsic

169 T3/D835Y, and Tel-PDGFRbeta, all can inhibit apoptosome function.

170 Thus, the Apaf-1 apoptosome functions as a proteolytic-based 'molecular t

171 sociate with and prevent the function of the apoptosome, giving a more detailed picture of the threat

172 ocessed caspase-9 initially binds the Apaf-1 apoptosome in cytochrome c/dATP-activated lysates and co

173 ell lysates, but directly interacts with the apoptosome in cytochrome c/dATP-activated lysates.

174 ular framework to understand the role of the apoptosome in programmed cell death and disease.

175 reduction in the amount of caspase-9 in the apoptosome in the SKOV3 cell line was associated with di

176 Hsp90beta interacted weakly with the apoptosome in untransformed cells.

177 biochemical experiments, and analyses of the apoptosome in various cancers and other disease states,

178 is sufficient to activate the Apaf-caspase-9 apoptosome in vitro.

179 peratively blocks the cytochrome c-dependent apoptosome in vitro.

180 , and Apaf-1, an activating component in the apoptosome, in two human cancer cell lines, lung adenoca

181 Unlike in the related heptameric Apaf-1 apoptosome, in which each subunit needs to be conformati

182 expression levels of known inhibitors of the apoptosome, including heat shock protein 70, heat shock

183 for activating endogenous caspases, from an apoptosome-independent to an apoptosome-dependent pathwa

184 These data provide an explanation for apoptosome inhibition by activated leukemogenic tyrosine

185 ies offer new insights into the mechanism of apoptosome inhibition by F1L as well as novel probes to

186 ssing these kinases, the previously reported apoptosome inhibitor, Hsp90beta, bound strongly to Apaf-

187 es and suggest that alterations in Hsp90beta-apoptosome interactions may contribute to chemoresistanc

188 ch kinetic cooperativity in formation of the apoptosome is a key element ensuring bistability.

189 The apoptosome is a multiprotein complex comprising Apaf-1,

190 In response to cell death signals, an active apoptosome is assembled from Apaf-1 and procaspase-9 (pc

191 quent processing of caspases-3 and -7 to the apoptosome is blocked.

192 activity of Casp9-TM in the presence of the apoptosome is likely attributable to a markedly reduced

193 k functions, indicating that formation of an apoptosome is necessary, but not sufficient, for timely

194 Once assembled, the apoptosome is relatively insensitive to the effects of i

195 significantly increases the activity of the apoptosome, it does little to attenuate its sensitivity

196 e c and in the presence of ATP/dATP forms an apoptosome, leading to the recruitment and activation of

197 e that procaspase-9 homodimerizes within the apoptosome, markedly increasing its avidity for the comp

198 API as an apoptotic enhancer that stimulates apoptosome-mediated caspase activation.

199 as demonstrated by the near complete loss of apoptosome-mediated caspase-3 activity when a point muta

200 and induction of apoptosis do not depend on apoptosome-mediated caspase-9 activation in prototypical

201 We show herein that apoptosome-mediated cleavage of procaspase-9 occurs excl

202 Thus, the apoptosome mediates the formation of caspase-9 homo- and

203 The apoptosome model includes N-terminal domains of Apaf-1,

204 and procaspase-9, critical components of the apoptosome, or overexpressing only conformationally acti

205 deoxynucleoside metabolites to activate the apoptosome pathway may be an additional biochemical mech

206 e of the events that occur in the Drosophila apoptosome prior to and after receiving an apoptotic sig

207 It is assumed that the Apaf-1-caspase-9 apoptosome processes caspase-7 in an analogous manner to

208 s interaction delays formation of the active apoptosome, promoting cell survival during short bursts

209 form of cell death is controlled through the apoptosome proteins, Dronc and Dark, together with the I

210 Using a defined apoptosome reconstitution system with recombinant Apaf-1

211 The apoptosome recruits and activates caspase-9, which in tu

212 probes to understand the molecular bases of apoptosome regulation and turnover.

213 The dATP bound to apoptosome remained as dATP, not dADP.

214 which caspase-9 or Dronc is activated by the apoptosome remains unknown.

215 cytosol triggers assembly of the oligomeric apoptosome, resulting in dimerization and activation of

216 Assembly of the apoptosome results in the proteolytic cleavage of procas

217 ed simply by directing their zymogens to the apoptosome, ruling out the requirement for allosteric ac

218 shows that a single Dark ring and the Apaf-1 apoptosome share many key features.

219 s currently held assumptions about the human apoptosome structure.

220 ts and in a reconstituted procaspase 9/Apaf1 apoptosome system.

221 ophila Apaf-1 related killer (Dark) forms an apoptosome that activates Dronc, an apical procaspase in

222 dimer-driven assembly at the surface of the apoptosome--the "induced proximity" model.

223 Activation of caspase-9 by dimerization in apoptosomes then triggers a caspase signaling cascade.

224 that Tango7 collaborates with the Drosophila apoptosome to drive a caspase-dependent remodeling proce

225 p, we created an improved model of the human apoptosome using a crystal structure of full length Apaf

226 the activation of the mitochondria-dependent apoptosome was a major event in the degeneration process

227 e-9, that of Casp9-TM in the presence of the apoptosome was drastically reduced.

228 aspase-9 was activated, and formation of the apoptosome was required to support apoptosis, as demonst

229 Analysis of the Drosophila apoptosome, which comprises 16 molecules of the Dark pro

230 It is now well appreciated that the apoptosome, which governs caspase-dependent cell death,

231 nd dATP, Apaf-1 assembles into an oligomeric apoptosome, which is responsible for the activation of p

232 rizes into a heptameric complex known as the apoptosome, which recruits and activates cell-killing ca

233 either into heptameric caspase-9-activating apoptosome, which subsequently activates caspase-3 and c

234 iming, the end product of assembly is a holo-apoptosome with an acentric CARD-CARD disk and tethered

235 p9 that is incapable of forming a productive Apoptosome with Apaf-1.

236 ts in the release of cytochrome c that forms apoptosomes with Apaf-1 and caspase-9.

237 mogen potently induces formation of the Dark apoptosome, within which Dronc is efficiently activated.